1. Field of the Invention
The present invention relates to novel polymeric compositions and to their use in absorption of oils and, more particularly, this invention relates to the absorption of polar-substituted organic compounds from aqueous suspension or solution.
2. Description of the Prior Art
The well-known cholesterol problem in the Western World is believed to originate, at least to some extent, from the high fat content in the diet. Fatty degeneration of the inmost wall of the artery, atherosclerosis, is a common ailment linked to high levels of serum cholesterol. Gallstones, or the deposition of cholesterol and bile pigments in the gallbladder, is also believed to result from excessive levels of cholesterol in the hepatic bile. Another theory of gallstone formation is based not only on excessive cholesterol levels, but also on the ability of the gallbladder to properly dispel bile into the bile duct. Both theories recognize that high cholesterol concentration presents problems.
Enterohepatic circulation involves the movement of bile constituents from the liver, through the gallbladder, the intestines, absorption from the intestines, and passage back to the liver.
Many types of dietary materials or medicines have been reported effective in the removal of bile acids from the enterohepatic circulation, resulting indirectly in a reduction in serum and tissue cholesterol, the parent sterol of bile acids. Included in these materials are dextran and cellulose ion exchange resins, lignin, other polysaccharides, Cholestyramine, and a synthetic organic polymer composed of a basic anion exchange copolymer of tetraethylenepentamine and epichlorohydrin with approximately 1 out of 5 amine nitrogens protonated. Evidence has just recently been reported for the nonsurgical removal of gallstones by the feeding of large amounts of the bile acid, chenodeoxycholic acid.
Present medicinal approaches to reducing serum and tissue cholesterol levels in man are indirect. Intestinal reabsorption of bile acids, which are liver-produced derivatives of cholesterol, is reduced by administration of non-absorbable bile acid-binding polymers. The binding is accomplished by means of ion exchange on polymers bearing amine groups. For example, materials under study include various primary, secondary and tertiary ethylamine adducts of cellulose and other polysaccharides, a copolymer of tetraethylene pentamine and epichlorohydrin, and a quaternary ammonium styrene-divinylbenzene copolymer. The last polymer, known as Cholestyramine, has been in use medically for a number of years.
In a first approach to the development of a dietary additive capable of absorbing significant amounts of cholesterol from the dietary tract, a class of lighty cross-linked hydrocarbon, swellable polymers were developed. These polymers are the subject of my copending application Ser. No. 228,229, filed on Feb. 22, 1972. Though these polymers demonstrated significant absorption of diverse types of oils, when tested with a model bile, there was no absorption of significant amounts of cholesterol and/or bile acid from the solution. It was determined that the absorption of lipids from bile is a wholly different process than absorption directly from the same lipids in bulk or simple solution state.
A hypothesis was first generated to explain the anomalous behaviour of the oil absorbing polymers. The model bile is composed of water and the lipids, lecithin, cholic acid, and cholesterol; the total lipid content is about 50% by weight. Although this solution appears to be completely homogeneous, even microscopically, the distribution of these four components is not uniform on a molecular scale. The water is continuous but the lipids exist in clusters of a few molecules each. These clusters are called micelles. A stable structure is produced in micelles because of the existence of both polar and nonpolar groupings in the two lipids lecithin and cholic acid. In both molecules, the nonpolar groupings are hydrocarbon. Hydrocarbons and water are generally immiscible. On the other hand, polar organic compounds tend usually to be very soluble in water. Thus, the structure envisioned for micelles is a tiny sphere in which these several molecules are oriented so as to surround a hydrocarbon interior by a polar shell.
Conceptually, there is no reason to expect a micelle's polar surface to have affinity for the hydrophobic surfaces of immersed oil-absorbing polymer particles. More to be expected is the operation of the polar shell as a barrier which either prevents or greatly reduces the opportunity for hydrocarbon groups inside the micelle to make contact with the polymer.
The formation of mixed micelles is of primary importance in the digestion of fats. Micelles are molecular aggregates composed, in this case, of bile salts, lecithin and cholesterol. A highly polar exterior portion of the micelle is water-soluble while the nonpolar interior is lipid-soluble. A relatively nonpolar material like cholesterol is solubilized by the micelle through the affinity of the lipophilic interior for cholesterol and the hydrophilic exterior for water, the continuous phase.
An understanding of the role of the mixed micelle in lipid digestion and assimilation leads to a theory of a polymer formulation -- formulation for materials with a high affinity and absorptive capacity for lipids. It is noted that the polar exterior of the micelle shields to some extent the nonpolar interior from the attraction of oleophilic materials. Therefore, micellar cholesterol or other nonpolar lipids would not even be aware of the presence of nonpolar materials outside the micelle. This would appear significant when considering polymers for lipid absorption.
A polymer comprised totally of hydrophilic chains would have great affinity for the continuous phase and the polar exterior of the micelle. However, disruption of the micelle prior to or during absorption would expose nonpolar constituents, for which the polymer would have no affinity. On the other hand, a totally oleophilic polymer would have no affinity for the polar groups of lipid molecules, nor would they have sufficient affinity for their hydrocarbon chain parts to draw the highly hydrophilic ends out of the aqueous phase.